HIV infection is a risk factor for rapid progression of a recently acquired tuberculosis (TB) infection and for re-activation of latent TB infection (LTBI). Because of the associated higher risk of mortality, tests that detect M. tuberculosis infection and disease at early stages are needed. The Tuberculin skin test (TST) with purified protein derivative (PPD), the most widely used technique for diagnosing LTBI, is inaccurate and inconvenient. The long term goal of the Project is to assess the usefulness of in vitro assays of cellular immunity such as the Interferon-g release assay (IGRA), in response to selected antigens of M. tuberculosis, in those with HIV infection. Earlier veterinary and human studies indicate good correlation between TST and IGRA, as well as higher positivity for IGRA than TST. More recently, RD1 (region of difference 1) gene products such as ESAT-6 and CFP-10 have served as specific M, tuberculosis antigens, without interference from prior BCG vaccination. While these tests may be useful in non-endemic countries, their utility in countries like India, with high prevalence of both tuberculosis and HIV infection, is yet to be established. The specific aims of the Project are: 1) To investigate whether IGRA could serve as an accurate marker of LTBI in an area of high TB and HIV prevalence. This will be achieved by carrying out IGRA, using the RD1 region antigens, ESAT-6 and CFP-10, in our endemic population with and without HIV infection. 2) To define the usefulness of IGRA in diagnosing active tuberculosis disease, in those with and without HIV infection. The IGRA results in the study groups with disease, TB and HIV-TB will be used. 3) To analyze whether IGRA will be a better and more useful indicator of LTBI than TST, in those with and without HIV infection. We will also make use of the results of "follow-up" testing to decide which is a more accurate test. IGRA, if found useful, will form a simple field test for application in Tuberculosis Control Program, as well as to target the HIV positive subjects for chemoprophylaxis. [unreadable] [unreadable] [unreadable]